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Source: American Association For Cancer Research Date: November 13, 2006 Multiplexed Serum Markers Screening For Detection Of Pancreatic Cancer A panel of 10 blood biomarkers performed almost perfectly in picking out people who had pancreatic cancer from those who didn't, according to researchers at the University of Pittsburgh. The advance raises hopes that a test can be developed to screen for the aggressive cancer in time to treat it, they say. -------------------------------------------------------------------------------- "Early detection of pancreatic cancer is crucial to survival, but there has been no way to diagnose it early before symptoms occur," said the lead investigator, Anna E. Lokshin, Ph.D., an associate professor of medicine AND pathology at the University of Pittsburgh School of Medicine. "This assay represents a new way to screen for disease that appears to be applicable to pancreatic cancer, AND potentially, to other cancer types." The assay contains the largest panel of blood-based biomarkers to be examined simultaneously in pancreatic cancer. It consists of proteins known to be secreted by pancreatic tumors as well as proteins that represent the body's response to that tumor growth, Lokshin said. "Tumors are located in the context of certain tissues, AND those tissues react in their own individual ways to the cancer," she said. "For example, tissue-specific proteins try to fight the cancer, AND each tumor type grows blood vessels in tissue uniquely, so we believe the body responds differently to each kind of cancer." The researchers initially evaluated a panel of 44 protein biomarkers, including cytokines, chemokines, adhesion molecules AND hormones, AND used blood from 100 pancreatic cancer patients AND a control group of 400 healthy people to find those associated with the cancer. They used a microbead array, which can sample up to 100 different proteins simultaneously, AND found 10 biomarkers that offered the highest diagnostic power, Lokshin said. Two of those biomarkers are CA125, which can detect a number of cancers but which is not very specific, AND CA19-9, which has been known to correlate weakly with pancreatic cancer. They found that this panel of markers correctly identified pancreatic cancers 97 percent of the time, with a sensitivity of 95 percent (meaning it could correctly identify cancerous lesions) AND with a 98 percent specificity (the ability to detect truly negative cases). The researchers are continuing to study, validate, AND perfect the assay, AND test its ability to identify pancreatic cancer at early, treatable stages. Although pancreatic cancer is relatively rare, survival is poor compared to most other forms of cancer - it is the fourth leading cause of cancer-related deaths in males AND the fifth-leading cause of cancer-related deaths in females. A diagnostic screen for pancreatic cancer would likely first be used in smokers, because use of tobacco is a known risk factor for developing pancreatic cancer, Lokshin said. The researchers also are developing similar assays for ovarian, breast, lung, endometrial, head AND neck, AND esophageal cancers. "So far, every panel is different for each cancer to the point where we can say with greater than 97 percent certainty which cancer it is," she said. "Surprisingly, although in theory body response could be similar for several cancers, in practice it is very different."

American Association For Cancer Research Date: November 13, 2006 Fusion Prostate Cancer: An Early Molecular Event Associated With Invasion The presence of a gene fusion in prostate tumors is significantly associated with aggressive cancer, metastatic spread, AND an increased probability of death, a team of researchers is reporting. -------------------------------------------------------------------------------- They say that the new gene, formed by the fusion of TMPRSS2 AND ERG, may serve as a biomarker to separate patients who might benefit from radical prostate cancer therapy from those who potentially need little, if any, treatment. "We believe this gene has the potential to be used as a diagnostic AND prognostic test, which could offer thousands of patients peace of mind AND spare them from unnecessary surgery AND therapy," said the study's lead author, Sven Perner, M.D.,, a postdoctoral fellow in the Department of Pathology at Harvard University's Brigham AND Women's Hospital in Boston. He worked with researchers from the Universities of California AND Michigan, Johns Hopkins University AND McGill University in Montreal. Perner AND his colleagues reported the discovery of the fused gene last year AND they now say that TMPRSS2-ERG occurs in about 50 percent of prostate cancers - making it the most common genetic aberration in human cancer, AND the first one found in a common solid cancer. Fused genes AND chromosomal rearrangements have been found in several blood cancers, such as chronic myelogenous leukemia (CML) AND in soft tissue tumors, such as Ewing's sarcoma, but these diseases are rare compared to prostate cancer, which is one of the leading cancers among American men. In this study, the researchers sought to learn whether TMPRSS2-ERG is associated with a particular prostate cancer stage, AND how it might be contributing to development of the cancer. They gathered 406 prostate tissue samples, representing a range of benign, precursor, AND malignant prostate lesions, AND used a FISH analysis to look for TMPRSS2-ERG. They didn't find any evidence of the fused gene in non-cancerous samples, but found it was present in 48.5 percent of localized prostate cancer tumors, 30 percent of hormone-naïve metastases, AND in 33 percent of hormone refractory metastasis, as well as in about 20 percent of prostatic intraepithelial neoplasias, a lesion believed to be precursor of invasive prostate cancer. The investigators also discovered that the gene fusion could occur in two different ways. The genes, TMPRSS2, which is regulated by the male sex-hormone androgen, AND ERG, which is a potential oncogene, are located close to one another on chromosome 21. When fused, TMPRSS2 drives over-expression of the ERG gene. According to Perner, fusion can occur when the piece of DNA separating the genes breaks off AND the genes merge (a process described as "fusion through deletion"), OR if parts of each gene break off AND switch positions ("translocation"). They found that TMPRSS2-ERG fusion through deletion was more common in the tumor samples as compared to TMPRSS2-ERG fusion through translocation. More recent work has found a significant association between TMPRSS2-ERG fusion AND death from prostate cancer, although the researchers have not yet been able to determine which fusion form predicted the highest risk of death. Perner says investigators are hoping to find a small molecule to inhibit the TMPRSS2-ERG fusion protein in the same way that the drug Gleevec has revolutionized care of CML.